The statements in this section merely provide background information related to the present disclosure and may not constitute prior art.
During chemotherapy, chemotherapeutic agents are typically injected intravenously. Intravenous injection, however, as a method of chemotherapy, has a number of potential disadvantages. These include delivery of potentially toxic chemotherapeutic agents to non-target regions of the body and a requirement for high doses of chemotherapeutic agents due to dilution, metabolism, and degradation of the drug throughout the body. Therefore, the injection of a drug directly into a target region affected by disease is desirable.
A number of diseases afflict the bone marrow specifically. These include leukemia, lymphoma and multiple myeloma, among others. These cancers are typically treated by intravenous chemotherapy. The intravenous method of delivery suffers from the limitations of intravenous therapy discussed above. Vascular injection results in only a small percentage of the agent reaching the target organ, or in this case, the marrow. This can lead to detrimental side effects due to the amount of agent necessary to inject into a vascular environment in order for an effective amount to reach the marrow. Thus, there is a need for improved devices and methods for effectively injecting therapeutic agents directly into the marrow.
Direct injection of chemotherapeutic agents into the bone marrow is not a method that has been established in the art. The use of needles to penetrate the bone to aspirate bone marrow is well-known in the art. Bone marrow aspiration is a procedure used to obtain the blood-forming portion (marrow) of the inner core of bone for examination in a laboratory or for transplantation. The procedure often includes inserting a needle into a bone that contains marrow and withdrawing the marrow.
The needles available for aspiration of bone marrow are not sufficient for the injection of therapeutic agents into the sternal bone marrow. Therefore, there is a need for a needle designed specifically for intramarrow injection/infusion that can also remain in the marrow for an extended period of time, such as a week or longer.
In order to determine whether intramarrow injection could be an effective method of treating bone marrow disease, initial studies in understanding bone marrow pathology in normal and diseased condition were conducted. (Islam A. 1982. Ph.D. Thesis. University of London.) These early studies resulted in a new method of fixing bone and bone marrow biopsies in a special fixative. Specimens fixed in Schaeffer's solution provides better cytomorphological details and specimens fixed in Bouin's solution are optimal for cytochemical and immunological studies, when compared to conventional 10% formalin.
Following fixation the bone and bone marrow biopsies were processed in plastic (methyl and glycol methacrylate) and semi-thin sections (1-2 micron thick) were obtained from these plastic embedded bone and bone marrow biopsies (BMB) using a special microtome. Unlike the conventional paraffin embedded biopsy sections which are thick (5-10 micron), these semi-thin sections of plastic embedded bone and bone marrow biopsies, when stained with Romanowsky stain, provide cellular morphology and structural details of the marrow in much greater detail than hitherto possible.
Research conducted by Islam using the plastic embedding method, resulted in the observation that the interface between the bone and marrow is not dissociated/separated but remains intact and the endosteal cells which line the bony trabeculae were clearer and did not become deformed or displaced like the cells would using the existing and conventional formalin fixed paraffin embedding method. The clear picture, close to what is observed in situ, of cell biology in the bone marrow produced by these studies showed for the first time the significance of the endosteal region in the origin and the spread of leukemia (Medical Hypothesis 39: 110-118 (1992), Leukemia Research 9:(11) 1415-1432 (1985)).
Based in part on observations of the endosteal cells in plastic embedded BMB sections from normal adults as well as from patients with various hematological disorders such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and myelodysplastic syndrome, Islam postulated that the endosteal cells are reminiscent of embryonal stage mesenchymal cells and, depending on the needs of the body, may differentiate into either myeloid, lymphoid, stromal or fat cells. Further, the endosteal cells may become osteoclasts and osteoblasts (bone forming cells). In leukemias, particularly in acute myeloid leukemia (AML), Islam observed that the leukemic blast cells in AML were originating from the endosteal region. In some instances the endosteal cells appeared to be giving rise to the leukemic blast cell population (Medical Hypothesis 39: 110-118 (1992), Leukemia Research 9:(11) 1415-1432 (1985)).
These observations prompted investigation into a potential treatment of leukemia through injection of chemotherapeutic agents directly into the marrow cavity, where leukemia originates, rather than the conventional intravenous method of delivery. Intramarrow injection of drugs could potentially improve delivery of the drugs to the necessary cells, thereby improving the outcome and response to therapy for such patients.